Impact of double versus single blastocyst biopsy and vitrification on clinical and neonatal outcomes in PGT cycles: A systematic review and meta-analysis of embryo retesting.

INTRODUCTION: As PGT advances in assisted reproduction, more embryos with inconclusive results, yet potentially transferable, have emerged. Current studies reveal a disparity between the reproductive potential of retested blastocysts and the supporting evidence. This systematic review and meta-analysis compared clinical outcomes of rebiopsied and revitrified blastocysts with those biopsied and vitrified once.

MATERIAL AND METHODS: Searches were conducted on June 26, 2024, across PubMed, EMBASE, Cochrane Library, Scopus, Web of Science, and Google Scholar, using thesaurus and free-text terms. Selection, data extraction, and risk of bias were assessed by three independent reviewers. The primary outcomes were live birth rate (LBR) and singleton birthweight; secondary outcomes were clinical pregnancy rate (CPR), clinical pregnancy loss rate (CPLR), positive pregnancy rate, very early pregnancy loss rate, and neonatal outcomes. Quantitative analyzes were performed using a random-effects model, pooling dichotomous outcomes as odds ratios (OR) and 95% CI and continuous outcomes as mean differences (MD) using the inverse variance model. Subgroup analyses based on "biopsy day" and "morphological grades" were performed.

RESULTS: Seventeen studies were included, reporting 36,441 SET cycles. Very low-quality evidence suggests that rebiopsy and revitrification were associated with a decreased likelihood of LBR compared with single biopsy and vitrification (OR = 0.54, 95% CI = 0.44-0.67; I2 = 12%; p < 0.00001, Pred Int = 0.38-0.79; 13 studies). No effect of retesting was found on the birthweight of 141 newborns (MD = 21.05, 95% CI = -64.83-106.94; I2 = 0%; p = 0.63, six studies). The odds of pregnancy were decreased for both positive pregnancy (OR = 0.58, Pred Int = 0.30-1.12; I2 = 41%; p = 0.001, eight studies) and CPR (OR = 0.60, 95% CI = 0.51-0.70; I2 = 0%; p < 0.00001, 14 studies), leading to a higher CPLR (OR = 1.56, 95% CI = 1.14-2.12; I2 = 0%; p = 0.005, 13 studies). No statistically significant subgroup effects were detected; however, the "biopsy at D5" and "high-quality" subgroups showed 10%-20% higher odds of LBR, which may hold clinical value and warrant further investigation.

CONCLUSIONS: Decision-making on retesting embryos for PGT should be done with caution, as it might reduce live birth rate in order to obtain the precise genetic diagnosis. Larger and well-designed studies, controlling for the main sources of bias, are still needed in order to improve the quality of the available evidence.